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Evaluation of different 15N-tracer substances for calculation of whole body protein parameters in infants.

The validity of using different 15N-tracer substances to measure whole body protein parameters, i.e., protein synthesis, protein breakdown, net protein gain, protein turnover, metabolic pool, and reutilization, was assessed by comparing the results obtained with: [15N]glycine, a mixture of 10 15N-labeled amino acids, and a 15N-labeled chicken egg protein in two infants, 9 and 12 weeks old, who were fed human milk. The tracer substances were fed orally as a single dose corresponding to a 15N-excess quantity of 0.2 mmol X kg-1 body weight. 15N Excretion in the urine was measured cumulatively by emission spectrometry, and the data on the protein metabolism were calculated by means of a three-pool model. All three tests yielded consistent net protein gains. The protein synthesis, protein breakdown, protein turnover, and nitrogen reutilization values produced by the [15N]glycine tracer study were higher than those produced by application of the 15N-amino acid mixture and the 15N-labeled egg protein. However, in our opinion, this discrepancy does not justify the replacement of [15N]glycine by expensive 15N-amino acid mixtures as tracer substances.

Amino Acids↗

Effect of two carbohydrate:lipid ratios of diets enterally fed to chronic alcoholics.

An amino acid mixture and different energy sources were enterally fed to 14 malnourished alcoholic patients in a metabolic unit. The patients were divided into three groups: Gp I received as enteral feeding the amino acid mixture plus carbohydrates; Gp II received the same mixture plus lipids and carbohydrates; and Gp III (control) was placed on a solid-food general hospital diet. The results were evaluated by measurement of plasma amino acids and by metabolic studies of nitrogen balance. No significant differences in plasma levels of amino acids were observed for any of the three groups between admission and discharge. The nitrogen absorption and digestibility of the amino acid mixtures offered to Gp I and Gp II was significantly higher than that of the controls. No effect of the energy source on nitrogen absorption, digestibility or retention was observed. The results suggest that the amino acid solution used was well utilized by the alcoholic patients and that the energy source (carbohydrates alone or carbohydrates plus lipids) was not a critical factor in the nitrogen utilization by the chronic alcoholic patients studied.

Adult↗

Stimulation of hepatic and renal ornithine decarboxylase activity by selected amino acids.

The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, increases after a protein meal. The effect of amino acid mixtures on hepatic and renal ODC activity and polyamine content was studied in postabsorptive and 72-hour fasted rats. Fasting decreased ODC activity in liver and in kidney by approximately 50%. Hepatic ODC activity increased tenfold 4 hours after intraperitoneal injection of either 1 g/kg of a synthetic mixture of 17 amino acids or of casein hydrolysate to fed rats and about 20-fold in fasted rats. Renal ODC activity increased four- and tenfold respectively. A mixture of glutamate, aspartate, and alanine at concentrations given in the hydrolysate reproduced the full amino acid effect. No amino acid was effective when given alone, nor were mixtures of the other amino acid constituents of the hydrolysate. Glutamate + alanine was ineffective as were glucose or various combinations of arginine, ornithine, aspartate and NH3. Ornithine + glutamate or aspartate + glutamate were active but stimulated less than aspartate + glutamate + alanine. Hepatic and renal putrescine content increased in parallel with ODC activity. The data suggest that specific amino acids possess the full ODC-stimulating capability of a high quality protein and that polyamine synthesis is linked to urea cycle activity.

Amino Acids↗

Further studies on the hypocholesterolaemic effect of soya-bean protein in rats.

1. The hypocholesterolaemic effect of soya-bean protein compared with that of casein, when fed at 200 g/kg diet for 3 weeks, was studied in rats. 2. Using a cholesterol-free low-fat (10 g maize oil/kg) diet, the hypocholesterolaemic effect was demonstrated not only with soya-bean protein but also with an amino acid mixture simulating this protein. The addition of lysine to these diets did not modify their intrinsic effects on serum cholesterol. 3. By feeding the vegetable protein or its amino acid mixture, both high-density-lipoprotein-and very-low-density-lipoprotein plus low-density-lipoprotein-cholesterol decreased to a similar extent, and the concentration of serum apolipoprotein A--I decreased and that of apolipoprotein B increased. 4. Although rats given soya-bean protein excreted more neutral and acidic steroids, the difference disappeared when the amino acid mixture was fed, indicating that the hypocholesterolaemic effect of the vegetable protein is not ascribed only to the increased elimination of steroids. 5. It is likely that the difference in the amino acid composition between animal and vegetable proteins is in fact responsible for the different response of serum cholesterol.

Amino Acids↗

Amino acid supply and protein metabolism in Ehrlich ascites tumour cells. 1. Identification of limiting amino acids.

The uptake and intracellular accumulation of an amino acid mixture by incubated Ehrlich ascites tumour cells was studied. The composition of the amino acid mixture simulated that of mouse intraperitoneal fluid and amino acid uptake was studied over a range of concentrations between 0.0 (no added amino acids) and 10.0-times intraperitoneal concentrations. For most amino acids uptake into cells and intracellular accumulation occurred as concentrations were increased up to 6.0-times the intraperitoneal concentrations; further increases in external amino acid concentrations did not increase concomitantly with intracellular concentrations. These data, when analysed indicated a net protein synthetic rate of 20% d-1 and that the rate of protein synthesis may be limited by the availability of the amino acids lysine, threonine and methionine.

Amino Acids↗

Liver and plasma copper concentrations in rats fed diets containing various proteins.

The question was addressed whether the type of dietary protein influences copper (Cu) concentrations in liver and plasma of rats. For this purpose, weanling female rats were fed diets containing as the sole source of protein either soybean protein, casein, amino acid mixtures simulating soybean protein or casein, lactalbumin, ovalbumin, or herring meal. The diets were balanced for residual Cu in the protein preparations. The type of protein and the composition of the amino acid mixture did not differentially influence liver Cu concentrations. Liver Cu was significantly lowered after feeding the amino acid mixtures when compared with the intact proteins. Plasma Cu concentrations were not affected by the type of protein in the diet.

Amino Acids↗

[Physicochemical parameters of rat liver chromatin during nonhormonal induction].

The changes of RNA-polymerase activity of hepatocytes nuclei, chromatin circular dichroism (CD) spectra and differential melting curves of hepatocytes of rats which were injected hydrocortisone or amino acid mixture intraperitoneally have been studied. Actinomycin D reduces essentially RNA-polymerase activity and maximum of CD spectra. Under the influence of hydrocortisone or amino acid mixture the inhibiting action of antibiotic is taken off but the RNA-polymerase activity and maximum of CD spectra don't achieve the meanings found under the influence of inductors only. The antibiotic injection changes essentially the chromatin melting parameters. A conclusion has been drawn that the amino acid mixture and hydrocortisone effect the transcription process affecting the different levels of chromatin structure.

Amino Acids↗

[The effect of the administration of an amino acid solution containing acetate on the calcium balance in surgical patients].

A frequent trouble in total parenteral nutrition is the occurrence of a negative calcium balance, due to reduction of calcium tubular reabsorption in acidosis. This condition could depend on acid metabolites raise, coming from degradation of nutritional amino acid mixtures. Authors have evaluated the effect of acetates addition to amino acid solutions on calcium balance. In fact the bicarbonate excess could reduce calcium urinary excretion. Thirty surgical patients have been treated. They were randomized according to acetates presence or absence in the administered solutions. In the acetate-treated group authors noted a raise in plasma bicarbonate and pH and a reduction in urinary calcium excretion. Adding acetates to amino acidic mixtures could reduce in total parenteral nutrition the risk of hypercalciuria and its related complications.

Acetates↗

A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function.

RATIONALE: We have previously shown in healthy volunteers that an amino acid mixture lacking tyrosine and phenylalanine reduces tyrosine availability to the brain and produces cognitive and neuroendocrine effects consistent with reduced dopamine function. This could provide a potential nutritional approach to disorders such as mania and schizophrenia, which are characterised by overactivity of dopamine pathways. The amino acid mixture we tested previously is unpalatable, whereas mixtures containing only branch chain amino acids can be made more palatable. However, the effects of such mixtures on dopamine function in humans have not been studied. OBJECTIVE: To assess the tolerability of different doses of branch chain amino acids and to measure their effects on neuroendocrine and cognitive measures sensitive to changes in dopamine function. METHODS: We used a randomised, double-blind, cross-over design in 12 healthy volunteers to assess the effect of single oral doses of 10 g, 30 g and 60 g branch chain amino acids on plasma prolactin and a test of spatial recognition memory RESULTS: The branch chain amino acids were well tolerated. The availability of tyrosine for brain catecholamine synthesis decreased in a dose-related manner. As hypothesised, the drink increased both the plasma prolactin and the latency to respond on the spatial recognition memory task. CONCLUSIONS: A drink containing branch chain amino acids is well tolerated in healthy volunteers and produces effects consistent with lowered dopamine function.

Adult↗

[Semiessential and nonessential amino acids in parenteral feeding].

With reference to a critical study of the relevant literature and to results from their own investigations, the authors emphasize the importance of the semi-essential and non-essential amino acids arginine, histidine, tyrosine, cystine and glutamic acid for the completion of essential amino-acid mixtures destined for parenteral feeding. MADDEN'S assumption that intravenously applied glutamic acid is intolerable was not supported by the authors' experiments in dogs. As evidenced by the increase of blood urea, the glutamic acid-containing amino-acid mixture was well utilizable. When glutamic acid is present, proline and alanine are obviously superfluous in amino-acid mixtures for parenteral feeding, since they are easily formed from glutamic acid by intermediary metabolism.

Administration, Oral↗

Effect of parenteral amino acids on leucine and urea kinetics in preterm infants.

OBJECTIVE: To examine the effect of two commonly used parenteral alimentation amino acid mixtures on whole-body leucine and urea kinetics. METHODS: Ten stable preterm infants were studied during the first 4 weeks after birth. Six infants received a mixture containing higher branched-chain amino acids, lower glycine plus added dicarboxylic acids formulation (Trophamine), and four received a standard amino acid mixture (Aminosyn). Whole-body protein turnover was measured with (1-13C)leucine tracer, and the rate of oxidation of protein was calculated by quantifying the appearance of carbon 13 from leucine in carbon dioxide as well as from rates of urea synthesis estimated by using (15N2)urea tracer. Energy consumption and substrate oxidation were quantified by indirect respiratory calorimetry. Infants were given similar quantities of energy (approximately 61 kcal/kg per day), glucose (approximately 10.7 mg/kg per minute) and protein (approximately 2.1 gm/kg per day). RESULTS: There was no significant difference in the rate of appearance of leucine in the two groups. However, the fraction of leucine oxidized (p = 0.002) and total rte of oxidation of leucine was higher in the Trophamine group. Thus additional branched-chain amino acids resulted in an increased contribution of C-1 of leucine to expired CO2. The rate of urea N synthesis was also similar in the two groups (Trophamine: 2.92 +/- 0.87 mg N/kg per hour; Aminosyn: 2.70 +/- 1.18 mg N/kg per hour). CONCLUSIONS: Although the use of Trophamine normalizes the blood amino acid pattern, it does not appear to improve nitrogen/protein kinetics. Furthermore, the additional branched-chain amino acids are disposed of by increased oxidation.

Amino Acids↗

Effect of acute tryptophan depletion on behavioral, cardiovascular, and hormonal sensitivity to cholecystokinin-tetrapeptide challenge in healthy volunteers.

Recent data suggest that serotonergic (5-HT) mechanisms may mediate the anxiogenic effects of cholecystokinin (CCK)-related peptides. Accordingly, we investigated the effect of lowering plasma tryptophan to the elicitation of behavioral, cardiovascular, and hormonal changes in healthy volunteers challenged with the tetrapeptide CCK agonist, CCK-4. Forty men without personal or family history of psychiatric disorders were randomly assigned to either a tryptophan-free amino acid mixture, which decreases central 5-HT concentrations, or a control mixture. Five hours after administration of the amino acid mixture, all subjects received a single intravenous injection of CCK-4. The main finding of the study was that acute depletion of tryptophan failed to modify the panicogenic and cardiovascular effects of CCK-4, although it did enhance CCK-4-mediated increases in ACTH/cortisol and prolactin secretion. While these findings suggest that at least part of the neuroendocrine action of CCK-4 is mediated through the 5-HT system, the locus of the 5-HT-CCK interaction and the specific 5-HT receptor subtype involved remains to be determined.

Adolescent↗

Pancreozymin bioassay in man based on pancreatic enzyme secretion: potency of specific amino acids and other digestive products.

The ability of products of digestion to stimulate pancreozymin secretion in man was investigated using a bioassay procedure, based on duodenal perfusion, which quantified the total outputs of pancreatic enzymes evoked by intraduodenal stimuli under steady-state conditions. Patterns of response resulting from physiologic intraduodenal concentrations of test material were basal output (with isotonic saline), washout of enzymes (with dextrose, micellar fatty acid, and amino acids), and sustained output of enzymes (with amino acids and micellar fatty acid). The sustained secretion of pancreatic enzymes found during the 2nd hr of perfusion and subsequently was characteristic of pancreozymin-induced secretion. The enzyme output in response to a mixture of essential and nonessential amino acids was significantly higher than that evoked by micellar fatty acid and was comparable with that resulting from the maximally tolerated dose of pancreozymin given by vein. Perfusion with essential amino acids caused enzyme outputs comparable to those induced by perfusion with the original amino acid mixture, whereas perfusion with nonessential amino acids had no effect. When the essential amino acids were tested individually, only phenylalanine, methionine, and valine caused significant increases in pancreatic enzyme output; the effect of tryptophan was indeterminate. However, the pancreatic enzyme output was less in response to these three essential amino acids than to mixtures containing all of them.

Adult↗

Mood response to acute tryptophan depletion in healthy volunteers: sex differences and temporal stability.

We investigated (1) the mood response of normal women, without a family history of major affective disorder, to acute tryptophan depletion, and (2) the temporal stability of the mood change, within subjects, when rechallenged at least 1 month later. To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested. The control treatment was a nutritionally balanced amino acid mixture containing tryptophan. A marked lowering of plasma tryptophan (80% to 90%) was achieved by both depletions. Compared to the balanced condition, the women exhibited a significant lowering of mood after the first tryptophan depletion on the elation-depression (p < .05), energetic-tired (p < .005), confident-unsure (p < .01), and clearheaded-confused (p < .01) scales of the bipolar profile of mood states. Whereas a lowering of mood was not found in a comparable sample of males studied earlier, these results were similar to those obtained in healthy males at genetic risk for major affective disorder (MAD). Inasmuch as a family history of MAD and female sex are predisposing factors to depression, these results suggest that a mood-lowering response to acute tryptophan depletion may occur preferentially in subjects with a susceptibility to lowered mood. However, the mood response to tryptophan depletion exhibited poor temporal stability in individual subjects.

Adolescent↗

Acute tryptophan depletion in bulimia: effects on large neutral amino acids.

Acute tryptophan depletion, which may reduce brain serotonin synthesis in humans, was evaluated in bulimic and normal subjects assessing its effects on the plasma ratio of tryptophan to the sum of the other large, neutral amino acids (TRP/sigma LNAA). Thirteen bulimic and 9 control women ingested an amino acid mixture containing either 2.3 g (control mixture) or 0 g of tryptophan (active mixture), in combination with 100 g of the other amino acids. Six healthy male volunteers were also studied, using a similar mixture containing 4.6 g of tryptophan. Bulimic and control women both experienced sizable reductions in the plasma TRP/sigma LNAA ratio, compared to baseline values, for both the active mixture (10% of baseline) or the control mixture (45% of baseline). For bulimic women, the active mixture produced a significant increase in fatigue and a trend toward increased anxiety and indecisiveness. The control mixture did not maintain baseline TRP/sigma LNAA ratios so we identified a control amino acid mixture that does not cause a drop in the plasma TRP/sigma LNAA ratio when ingested (4.6 g tryptophan in combination with 100 g of other amino acids). An oral, tryptophan-deficient amino acid mixture produced acute, substantial reductions in the plasma TRP/sigma LNAA ratio in all subjects, suggesting that the treatment should reduce brain tryptophan uptake and serotonin synthesis. A control mixture containing tryptophan was also identified that maintains the plasma TRP/sigma LNAA ratio at pretreatment values.

Adolescent↗

Multiple metabolic functions of glucose in rat pancreatic islets.

Metabolic interactions between glucose and amino acids were studied with isolated rat islets using glucose utilization and lactate formation as indicators. Certain amino acids (8-10 mM) are capable of greatly stimulating lactate formation from 5mM glucose. On a molar basis L-isoleucine is the most potent stimulator in a group of twenty-six amino acids. Aphysiological amino acid mixture (7.5-14 mM) or L-isoleucine (8 mM) profoundly altered the basic sigmoidal relation between glucose concentration in the medium and the rate of glucose utilization and lactate formation: with basal glucose (5 mM) both glucose utilization and lactate production were stimulated by the amino ACID MIXTURE and by L-isoleucine; at high glucose levels utilization was decreased by the amino acid mixture, but was unaffected by L-isoleucine, whereas lactate formation was decreased by both additions. The data indicate that amino acids may play a significant role in regulating the extent to which glucose serves as a fuel of pancreatic islet cells and in determining the pathways of glucose metabolism. In order to elucidate the mechanisms of the amino acid effect, studies with phloridzin, ouabain, iodoacetate, cytochalasin B, and Na+-deficiency were performed with the most effective amino acid, L-isoleucine. Each of these agents and Na+-deficiency substantially reduced or completely blocked the extra lactate formation induced by L-isoleucine (8-10 mM). The intracellular uptake of 14-CL-isoleucine by isolated islets was found to be Na+-independent, and uphill transport of this amino acid was not detectable, whether basal glucose was present in the medium or not. The action of iodoacetate in blocking glycolysis was reinvestigated. After forty-five minutes of exposure, 0.2mM iodoacetate completely blocks lactate formation as well as glucose utilization. Thisconfirms and extends earlier data for this laboratory and suggests that this SH-reagent indeed allows dissociation of the fuel and releasing functions of glucose.

Amino Acids↗

Qualitative manipulation of amino acid supply during total parenteral nutrition in surgical patients.

We investigated whether a qualitative manipulation of amino acid mixture could improve the nutritional status of patients undergoing surgery. Patients received total parenteral nutrition for 2 consecutive 5-day periods. Energy and nitrogen supplies were calculated using a modified Harris-Benedict equation, with an energy-to-nitrogen ratio of 125 kcal/g nitrogen (N). The mean kilocalorie lipids-to-glucose ratio was 35% to 65%. There were 6 patients in the control group and 7 patients in the experimental group. The control group received the same standard amino acid solution (Vintène, Baxter-Clintec, Maurepas, France) for the entire 10 days. The experimental group received the standard solution during the first 5 days but was switched to a more individualized solution during the last 5 days. The second solution was determined from a linear regression performed on day 3 comparing rate of infusion of each amino acid and its plasma variations after 3 hours of infusion with basal values. Amino acids were defined as oversupplied or undersupplied when not within the 95% confidence interval (above or below the curve, respectively). Daily nitrogen balance and urinary excretion of 3-methylhistidine were measured from day 1 to day 10 in all patients. For the patients in whom these measures were made, amino acid variations except those of lysine (11 of 12), ornithine (6 of 12), alanine (5 of 12), arginine (5 of 12), and glutamate (5 of 12) were within the 95% confidence interval. During the second 5-day period, imbalances persisted in the control group but were almost gone in the experimental group. Daily nitrogen balance was not significantly different between groups. However, when expressed as a mean over each period, nitrogen balance was significantly higher during the second period in the experimental group than in the control group: 4.5+/-0.8 g N/d versus 0.2+/-0.7 g N/d, p < .01. The ratio of urinary 3-methylhistidine to creatinine decreased from day 1 to day 10 in both groups. These findings suggest that the relationship between rate of infusion and plasma amino acid variation may offer a rational basis for choosing the most appropriate amino acid mixture for catabolic patients. An appropriate mixture would limit plasma amino acid imbalances and improve nitrogen retention. This therapy must now be tested in a larger population of patients.

Adolescent↗

Hypercholesterolemic responses in rabbits to selected groups of dietary essential amino acids.

In rabbits, elevation of LDL cholesterol is produced by feeding a cholesterol-free, semipurified diet containing 30% casein amino acid mixture, but not by feeding the same diet containing 14.7% of the casein amino acid mixture, corresponding to a normal level of dietary protein. The hypercholesterolemic response was greater when all essential amino acids except arginine or all ketogenic essential amino acids (lysine, leucine, isoleucine, threonine, phenylalanine, tryptophan and glycine) were selectively fed at three times the normal level. In the present experiments, the same high levels of lysine, leucine and methionine produced a substantial hypercholesterolemia, addition of either isoleucine + threonine or isoleucine + valine did not enhance the effect, and a mixture of threonine, histidine, phenylalanine, tryptophan and glycine gave only a moderate response. A combination of lysine and methionine produced a greater effect than either lysine and leucine or leucine and methionine. Hypercholesterolemic diets containing high levels of lysine and leucine did not cause significantly greater plasma ketone bodies or free fatty acids. Differences in growth rates and ketogenic responses were not generally correlated with hypercholesterolemia.

Amino Acids, Essential↗